Prostate gland & seminal vesicles

• Diagnostic criteria (Mod Pathol 2006;19:1528, Arch Pathol Lab Med 2007;131:1103, Am J Surg Pathol 2010;34:470, Arch Pathol Lab Med 2015;139:1234, Arch Pathol Lab Med 2021;145:461, Adv Anat Pathol 2021;28:276, Histopathology 2022;81:447)
  • Architecture
    • Solid growth
    • Dense cribriform pattern, characterized by more solid than luminal areas (> 50% epithelium relative to luminal spaces)
    • Inclusion of patterns with less complexity (i.e., loose cribriform and micropapillary, remain controversial)
  • Histologic features
    • Expansile epithelial proliferation in the preexisting duct acinar system
    • Retention of basal cell layer: continuous or interrupted
    • Enlarged nuclei
    • Nuclear atypia
    • Frequent, easily identifiable mitosis
    • Comedonecrosis

Contributed by Erica Vormittag-Nocito, M.D. and Andre Kajdacsy-Balla, M.D., Ph.D.

Which of the following is true regarding intraductal carcinoma of the prostate (IDC-P)?

1. Basal cell layer is not present in intraductal carcinoma
2. Intraductal carcinoma is a common finding in prostate biopsies
3. Intraductal carcinoma should be graded based on the Gleason pattern scoring system
4. PTEN mutations are common in intraductal carcinoma

D. PTEN mutations are common in intraductal carcinoma. Intraductal carcinoma commonly has PTEN deletions seen by IHC. PTEN loss is seen in 69 - 89% of IDC-P cases and loss of heterozygosity (LOH) of PTEN is seen in ~45% of IDC-P cases (Prostate 2016;76:394, Genes Chromosomes Cancer 2008;47:565). Answer C is incorrect because IDC-P without the presence of invasive carcinoma should not be assigned a Gleason grade. 2 differing recommendations exist regarding whether to grade or not when associated with invasive carcinoma: the 2019 Genitourinary Pathology Society (GUPS) does not favor including IDC-P into the Gleason score, while the 2019 ISUP favors it. The 2022 5th edition of the WHO classification of tumors of the urinary and male genital systems has not endorsed either of these positions (Eur Urol 2021;79:3, Eur Urol 2022;82:469). Answer B is incorrect because IDC-P is found in ~14% of prostate biopsies that harbor concomitant invasive carcinoma. The incidence of IDC-P in prostate biopsies without associated invasive carcinoma has been reported to be 0.06 - 0.26% (Mod Pathol 2006;19:1528, Histopathology 2013;63:574, Eur Urol 2017;72:492, Eur Urol 2022;82:469). Answer A is incorrect because IDC-P is characterized by the presence of peripheral basal cells that can be highlighted by IHC when appropriate (Mod Pathol 2006;19:1528, J Clin Transl Pathol 2023;3:26).

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Reference: Intraductal carcinoma

A 65 year old man had a radical prostatectomy for invasive carcinoma previously found on prostate biopsy. What do the above histology findings predict about this patient's clinical course?

1. Patient has a higher probability of biochemical recurrence
2. Patient is cured with prostatectomy alone
3. Patient was overtreated as he did not need a prostatectomy
4. Patient will do the same as other patients within his same grade group without this finding

A. Patient has a higher probability of biochemical recurrence. Patients with intraductal carcinoma have higher stage, higher grade tumors with higher likelihood of recurrence and do worse when matched for grade group. IDC-P is strongly associated with biochemical recurrence after radical prostatectomy (Eur Urol 2022;82:469). Answer B is incorrect because rebiopsy within 3 months or definitive therapy is recommended in isolated IDC-P without invasive carcinoma and in IDC-P with invasive low grade carcinoma. In IDC-P cases associated with a high grade invasive tumor, current guidelines recommend surgery and adjuvant therapy (Yonsei Med J 2016;57:1054, Virchows Arch 2019;474:525). Answer C is incorrect because, given the clinical significance of the presence of IDC-P and its association with aggressive disease, radical therapy is the current recommendation (Curr Oncol Rep 2021;23:110). Answer D is incorrect because IDC-P is considered an independent adverse prognostic factor and is frequently associated with high grade and high stage invasive prostatic adenocarcinoma. Comedonecrosis has been associated with worse histopathological features on prostatectomies and is an independent predictor of poorer clinical outcome (Yonsei Med J 2016;57:1054, Virchows Arch 2019;474:525, Histopathology 2022;81:447, Arch Pathol Lab Med 2023;147:94).

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Reference: Intraductal carcinoma